Interindividual differences in the psychotomimetic response to the N-methyl-d-aspartate receptor antagonist ketamine are commonly observed. The apolipoprotein E (APOE) ε4 allele has been associated with reduced severity of positive psychotic symptoms in schizophrenia. In this study, we sought to determine if the APOE ε4 allele influences the psychotomimetic response to ketamine in schizophrenics. Eighteen patients genotyped at the APOE locus underwent a double-blind infusion of ketamine and of placebo. Ketamine-induced alterations in the brief psychiatric rating scale factors were compared between schizophrenics with and without the APOE ε4 allele. APOE ε4+ schizophrenics displayed significantly reduced ketamine-induced psychosis, as compared to ε4- patients. These preliminary data indicate that the psychotomimetic response to ketamine may be genetically influenced and may provide additional evidence that APOE may modify expression of the positive symptoms in schizophrenia. Copyright (C) 1998 American College of Neuropsychopharmacology.
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